Plasma lipoprotein(a) size polymorphism and function: apo(a) subunit size determines galectin-1 recognition and apoB subunit epitope masking

Abstract

Polymorphism and pathological potential of human plasma lipoprotein(a) [Lp(a)] are determined solely by variation in size of its apo(a) subunit which is linked by a disulfide to an apoB subunit of invariant size. Affinity precipitation of Lp(a) from plasma employing the O-glycan-specific lectin jacalin before electrophoretic removal of adhering LDL was shown to be comprehensive without loss of lipoprotein structure. Isolation of even low abundance Lp(a) molecules by this protocol facilitated study of variations in subunit interactions as a function of Lp(a) size. Affinity of the autologous lectin galectin-1 toward Lp(a) isoforms increased with their size. Since apoB is not a ligand for galectin-1 result suggested apo(a) size as a modulator of Lp(a) adhesion in vivo to vascular cells and macrophages that express this lectin. Result may also explain the inverse relation of Lp(a) size to its rate of release from the galectin-1-rich intracellular compartments. N-Glycans and antigenic epitopes of apoB in Lp(a) were masked from recognition by the lectin concanavalin A and anti-apoB antibody respectively in proportion to the size of apo(a) . Recovery of apoB from masking upon removal of apo(a) alone from Lp(a) by dithiothreitol-mediated reduction was proportional to the size of the leaving apo(a). Since LDL receptors recognize lipoproteins through apoB epitopes results explain the reported lower binding of larger Lp(a) molecules to these receptors.